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Objective To investigate the effect and mechanism of interleukin (IL)-17C in mice undergoing kidney transplantation. Methods The life-supporting kidney transplantation mice models were established using Balb/c (H-2Kd) mice as the donors, IL-17C gene knock out (IL-17CKO) mice (knockout group) and C57BL/6J(H-2Kb) mice (wild group) were chosen as the recipients. The postoperative body mass and survival time of mice were statistically compared between two groups. Pathological examination of the kidney graft was performed by using hematoxylin-eosin (HE) staining and periodic acid-Schiff (PAS) staining. The expression levels of granzyme B, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-6 and IL-1β messenger ribonucleic acid (mRNA) in the kidney graft tissue were quantitatively measured by reverse transcription polymerase chain reaction (RT-PCR). The proportion of inflammatory cell infiltration in the kidney graft tissue was detected by flow cytometry. Results In the knockout group, the survival time of mice after kidney transplantation was significantly shorter than that of the wild mice (P=0.031). The body mass was more evidently decreased in the knockout group with no statistical significance from that in the wild group. Pathological examination demonstrated that the kidney graft injury in the knockout group was significantly worse than that in the wild group. The mRNA expression levels of granzyme B, IFN-γ, TNF-α, IL-6 mRNA in the knockout group were significantly up-regulated compared with those in the wild group (all P < 0.01). The mRNA expression level of IL-1β showed a decreasing trend with no statistical significance (P=0.16). Flow cytometry analysis revealed that the infiltration of CD45+CD11b+Ly6G+ neutrophil and CD45+CD11b+Ly6Chi monocyte in the kidney graft of knockout mice was significantly higher compared with that of the wild mice (P < 0.05, P < 0.01), whereas the infiltration of CD45+Ly6ChiF4/80+ macrophage did not significantly differ between two groups (P > 0.05). Conclusions IL-17C participates in the regulation of inflammatory response after kidney transplantation. It can alleviate acute rejection and improve the survival of kidney graft by down-regulating the expression of pro-inflammatory cytokines and infiltration of inflammatory cells.

Background: Serum fibroblast growth factor 23 (FGF23) is associated with acute kidney injury (AKI) and mortality in patients with critical illnesses. However, the accurate predictive performance of FGF23 on AKI remains inconclusive. Methods: Meta-analysis was performed using data sources including PubMed, Web of Science, EMBASE, and Cochrane (until June 1, 2021). Cohort or observational studies including patients with AKI and serum FGF23 level as the index test were included. The primary outcome was the AKI detective accuracy. This study has been registered in PROSPERO (CRD42021249930). Results: Eleven studies with 1946 patients in seven countries were included. Across all settings, the sensitivity and specificity for serum FGF23 levels to predict AKI were 82% (95% CI, 66-91%) and 77% (95% CI, 67-85%), respectively. The diagnostic odds ratio of FGF23 was 15.51 (95% CI, 4.89-49.19), with the pooled positive likelihood ratio of 3.62 (95% CI, 2.25-5.83) and a negative likelihood ratio of 0.23 (95% CI, 0.11-0.50). The area under the receiver operating characteristic curve to detect AKI was 0.86 (95% CI, 0.82-0.88). C-terminal FGF23 had a better performance than intact FGF23. Conclusions: Plasma FGF23 is a valuable biomarker for incident AKI in critically ill patients. Comparisons of FGF23 with other biomarkers in AKI still need more studies to prove.

Hailong Jin,1 Peijie Li,2 Chenyu Mao,3 Kankai Zhu,1 Hai Chen,1 Yuan Gao,1 Jiren Yu1 1Department of Gastrointestinal Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, People’s Republic of China; 2Department of Pathology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, People’s Republic of China; 3Department of Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, People’s Republic of ChinaCorrespondence: Yuan Gao; Jiren YuDepartment of Gastrointestinal Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Qingchun Road 79, Hangzhou 310003, People’s Republic of ChinaTel +86 571 8723 6147Fax +86-571-8707 2577Email ygao21@hotmail.com; yujr0909@zju.edu.cnAbstract: Programmed cell death-1 (PD-1) immune checkpoint inhibitors have exhibited promising efficacy in various types of tumors. Here, we report an unresectable locally advanced gastric cancer (GC) with programmed cell death ligand-1 (PD-L1) positive and microsatellite instability (MSI), which exhibiting an unexpected efficacy of pathological complete response (pCR) after a single dose of anti-PD-1 therapy in combination with chemotherapy as a first-line setting. A 66-year-old man diagnosed with gastric cancer and was clinically staged as cT4aN+M0. After one cycle treatment (oxaliplatin plus capecitabine plus anti-PD-1antibody), repeated computed tomography (CT) showed tumor shrinkage and the plasma carcinoembryonic antigen decreased dramatically. Curative distal gastrectomy with D2+ lymphadenectomy was performed and the pathological staging was pT0N0M0. Immunohistochemistry and polymerase chain reaction-based method revealed that the patient had a PD-L1 positive and MSI-high GC, while the Epstein-Barr virus was absent. Furthermore, much CD8+ tumor-infiltrating lymphocytes (TILs) were observed within the tumor and invasion front, which were responsible for tumor shrinkage, due to the recognition of abundant tumor neoantigens and their corresponding immune checkpoints. Our case report indicates that a combination of immunotherapy plus chemotherapy as a first-line treatment might offer a promising treatment option for locally advanced gastric adenocarcinoma with PD-L1 positive and MSI-high.Keywords: gastric cancer, immune checkpoint inhibitor, programmed cell death-1, microsatellite instability, chemotherapy

Presentation18857

Several studies in recent years have confirmed that the direct application of pulsed radiofrequency (PRF) on peripheral nerve compression points can alleviate hyperalgesia in animal models of neuropathic pain (NP). However, the mechanism underlying the treatment of peripheral nerves by PRF is unclear.We aim to observe changes in pain behavior after the application of PRF on the ligation site of the sciatic nerves (SNs) of rats with chronic constriction injury (CCI) and to investigate the effects of PRF on the transcription and translation levels of glial cell line-derived neurotrophic factor (GDNF) in nerve tissues at the treatment site.A randomized, experimental trial.Experimental Animal Center, Beijing Tiantan Hospital.Ninety-six adult male Sprague-Dawley rats were randomly divided into 4 groups: sham-sham (SS) group, sham-PRF (SP) group, CCI-sham (CS) group, and CCI-PRF (CP) group. The right SNs of rats in the CS and CP group were ligated to establish the CCI model. The right SNs in the SS and SP groups were isolated and exposed but without being ligated. On the fourteenth day after CCI/sham operation, PRF treatment was performed on the midpoint of the ligation sites of the SN in the CP group and the corresponding sites in the SP group. The electrode was only placed at the ligation sites of the SN in the CS group and the corresponding sites in the SS group without current being applied. The 50% paw withdrawal threshold (50%PWT) and thermal withdrawal latency (TWL) of rats in all of the groups were measured. The transcription and translation levels of GDNF of the PRF/sham treatment sites were measured before and after treatment by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assays (ELISAs).The 50%PWT value of the hind paws of rats in the CP group gradually increased on day 6 after the PRF treatment and was significantly higher than that in the CS group (6 days after treatment P0.05; 14 days after treatment P0.01). The TWL value in the CP group was higher than that in the CS group 2 days after treatment (P0.05) and was significantly higher (P0.01) from day 6 until the end of the experiment. On the day 6 and 14 after PRF treatment, the mRNA and protein expression levels of GDNF at the ligation sites of the SNs of rats in the CP group were higher than both the levels before treatment and those in the CS group (P0.01).The efficacy of PRF treatment in the CCI model was only tested within 14 days, and the changes in GDNF levels were only tested at 3 time-points before and after treatment.The direct application of PRF on SN ligation sites in the CCI model can safely and effectively alleviate NP. One of the mechanisms of this effect could be the upregulation of the transcription and translation of GDNF in compressed SNs.Pulsed radiofrequency, chronic constriction injury, sciatic nerve, 50% paw withdrawal threshold, thermal withdrawal latency, glia cell line-derived neurotrophic factor, reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay.

China's currency policy has been criticized for its apparent pursuit of mercantile advantage by artificially stimulating exports, which potentially have adverse effects on other economies. While China's currency policy may have positive output effects, there may be additional profits or losses. This paper computes the annual and cumulative accounting profits from currency intervention since 1994 when China began its currency intervention. It is shown that profits initially were positive but China since 2007 has lost a massive amount from the currency market.